Effects of etomidate combined with dexmedetomidine on adrenocortical function in elderly patients: a double-blind randomized controlled trial.

Etomidate has been advocated to be used in anesthesia for the elderly and the critically ill patients due to its faint effect on cardiovascular system. But the dose-dependent suppression of etomidate on adrenal cortex function leads to the limitation of its clinical application. Clinical research showed that dexmedetomidine could reduce the dose requirements for intravenous or inhalation anesthetics and opioids, and the hemodynamics was more stable during the operation. The objective was to observe the effect of etomidate combined with dexmedetomidine on adrenocortical function in elderly patients. 180 elderly patients scheduled for elective ureteroscopic holmium laser lithotripsy were randomly allocated to PR group anesthetized with propofol-remifentanil, ER group anesthetized with etomidate-remifentanil, and ERD group anesthetized with dexmedetomidine combined with etomidate-remifentanil. Patients in each group whose operation time was less than or equal to 1 h were incorporated into short time surgery group (PR1 group, ER1 group and ERD1 group), and whose surgical procedure time was more than 1 h were incorporated into long time surgery group (PR2 group, ER2 group and ERD2 group). The primary outcome was the serum cortisol and ACTH concentration. The secondary outcomes were the values of SBP, DBP, HR and SpO2, the time of surgical procedure, the dosage of etomidate and remifentanil administered during surgery, the time to spontaneous respiration, recovery and extubation, and the duration of stay in the PACU. The Serum cortisol concentration was higher at t1~2 in ERD1 group compared to ER1 group (P < 0.05). The Serum cortisol concentration at t1~3 was higher in ERD2 group than in ER2 group (P < 0.05). The Serum ACTH concentration was lower at t1~2 in ERD1 group compared to ER1 group (P < 0.05). The Serum ACTH concentration at t1~3 was lower in ERD2 group compared to ER2 group (P < 0.05). The SBP at T1 and T3 were higher in ER2 and ERD2 group than in PR2 group (P < 0.05). The DBP in ER1 and ERD1 group were higher at T1 compared to PR1 group (P < 0.05). The dosage of etomidate was significantly lower in ERD1 group and ERD2 group than in ER1 group and ER2 group (P < 0.05), respectively. The administration of dexmedetomidine combined with etomidate can attenuate the inhibition of etomidate on adrenocortical function in elderly patients and maintain intraoperative hemodynamic stability.

Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia.

BACKGROUND: Bronchopulmonary dysplasia is a prevalent complication after extremely preterm birth. Inflammation with mechanical ventilation may contribute to its development. Whether hydrocortisone treatment after the second postnatal week can improve survival without bronchopulmonary dysplasia and without adverse neurodevelopmental effects is unknown. METHODS: We conducted a trial involving infants who had a gestational age of less than 30 weeks and who had been intubated for at least 7 days at 14 to 28 days. Infants were randomly assigned to receive either hydrocortisone (4 mg per kilogram of body weight per day tapered over a period of 10 days) or placebo. Mandatory extubation thresholds were specified. The primary efficacy outcome was survival without moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age, and the primary safety outcome was survival without moderate or severe neurodevelopmental impairment at 22 to 26 months of corrected age. RESULTS: We enrolled 800 infants (mean [±SD] birth weight, 715±167 g; mean gestational age, 24.9±1.5 weeks). Survival without moderate or severe bronchopulmonary dysplasia at 36 weeks occurred in 66 of 398 infants (16.6%) in the hydrocortisone group and in 53 of 402 (13.2%) in the placebo group (adjusted rate ratio, 1.27; 95% confidence interval [CI], 0.93 to 1.74). Two-year outcomes were known for 91.0% of the infants. Survival without moderate or severe neurodevelopmental impairment occurred in 132 of 358 infants (36.9%) in the hydrocortisone group and in 134 of 359 (37.3%) in the placebo group (adjusted rate ratio, 0.98; 95% CI, 0.81 to 1.18). Hypertension that was treated with medication occurred more frequently with hydrocortisone than with placebo (4.3% vs. 1.0%). Other adverse events were similar in the two groups. CONCLUSIONS: In this trial involving preterm infants, hydrocortisone treatment starting on postnatal day 14 to 28 did not result in substantially higher survival without moderate or severe bronchopulmonary dysplasia than placebo. Survival without moderate or severe neurodevelopmental impairment did not differ substantially between the two groups. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01353313.).

Impact of Hydrocortisone and of CRH Infusion on the Hypothalamus-Pituitary-Adrenocortical Axis of Septic Male Mice.

PURPOSE: Sepsis is hallmarked by high plasma cortisol/corticosterone (CORT), low adrenocorticotropic hormone (ACTH), and high pro-opiomelanocortin (POMC). While corticotropin-releasing hormone-(CRH) and arginine-vasopressin (AVP)-driven pituitary POMC expression remains active, POMC processing into ACTH becomes impaired. Low ACTH is accompanied by loss of adrenocortical structure, although steroidogenic enzymes remain expressed. We hypothesized that treatment of sepsis with hydrocortisone (HC) aggravates this phenotype whereas CRH infusion safeguards ACTH-driven adrenocortical structure. METHODS: In a fluid-resuscitated, antibiotics-treated mouse model of prolonged sepsis, we compared the effects of HC and CRH infusion with placebo on plasma ACTH, POMC, and CORT; on markers of hypothalamic CRH and AVP signaling and pituitary POMC processing; and on the adrenocortical structure and markers of steroidogenesis. In adrenal explants, we studied the steroidogenic capacity of POMC. RESULTS: During sepsis, HC further suppressed plasma ACTH, but not POMC, predominantly by suppressing sepsis-activated CRH/AVP-signaling pathways. In contrast, in CRH-treated sepsis, plasma ACTH was normalized following restoration of pituitary POMC processing. The sepsis-induced rise in markers of adrenocortical steroidogenesis was unaltered by CRH and suppressed partially by HC, which also increased adrenal markers of inflammation. Ex vivo stimulation of adrenal explants with POMC increased CORT as effectively as an equimolar dose of ACTH. CONCLUSIONS: Treatment of sepsis with HC impaired integrity and function of the hypothalamic-pituitary-adrenal axis at the level of the pituitary and the adrenal cortex while CRH restored pituitary POMC processing without affecting the adrenal cortex. Sepsis-induced high-circulating POMC may be responsible for ongoing adrenocortical steroidogenesis despite low ACTH.

Prolonged cortisol elevation alters whole body and tissue metabolism in rainbow trout (Oncorhynchus mykiss).

Chronic elevation of circulating cortisol is known to have deleterious effects on fish, but information about the consequences of prolonged cortisol elevation on the metabolism of fish is scarce. To test the effects of chronic cortisol elevation on the aerobic performance of rainbow trout, we examined how two severities of chronically elevated plasma cortisol levels affected the oxygen uptake during rest and after exhaustive exercise using a high (HC) and a medium cortisol (MC) treatment. High cortisol doses significantly affected standard (SMR) and maximum metabolic rates (MMR) compared to control fish. In comparison, the medium cortisol treatment elevated maximum metabolic rates (MMR) but did not significantly influence SMR compared to a sham group (S) and control group (C). The medium cortisol treatment resulted in a significantly increased metabolic scope due to an elevation of MMR, an effect that was abolished in the HC group due to co-occuring elevations in SMR. The elevated SMR of the HC-treated fish could be explained by increased in vitro oxygen uptake rates (MO2) of specific tissues, indicating that the raised basal metabolism was caused, in part, by an increase in oxygen demand of specific tissues. Haematological results indicated an increased reliance on anaerobic metabolic pathways in cortisol-treated fish under resting conditions.

Adrenal Insufficiency at the Time of COVID-19: A Retrospective Study in Patients Referring to a Tertiary Center.

CONTEXT: Coronavirus disease 2019 (COVID-19) represents a global health emergency, and infected patients with chronic diseases often present with a severe impairment. Adrenal insufficiency (AI) is supposed to be associated with an increased infection risk, which could trigger an adrenal crisis. OBJECTIVE: Our primary aim was to evaluate the incidence of COVID-19 symptoms and complications in AI patients. DESIGN AND SETTING: We conducted a retrospective case-control study. All patients were on active follow-up and lived in Lombardy, Italy, one of the most affected areas. PATIENTS: We enrolled 279 patients with primary and secondary AI and 112 controls (patients with benign pituitary lesions without hormonal alterations). All AI patients had been previously trained to modify their replacement therapy on stress doses. INTERVENTION: By administering a standardized questionnaire by phone, we collected data on COVID-19 suggestive symptoms and consequences. RESULTS: In February through April 2020, the prevalence of symptomatic patients (complaining at least 1 symptom of viral infection) was similar between the 2 groups (24% in AI and 22.3% in controls, P = 0.79). Highly suggestive COVID-19 symptoms (at least 2 including fever and/or cough) also occurred equally in AI and controls (12.5% in both groups). No patient required hospitalization and no adrenal crisis was reported. Few nasopharyngeal swabs were performed (n = 12), as indicated by sanitary regulations, limiting conclusions on the exact infection rate (2 positive results in AI and none in controls, P = 0.52). CONCLUSIONS: AI patients who are adequately treated and trained seem to display the same incidence of COVID-19-suggestive symptoms and disease severity as controls.

Black Turmeric and Aloe Vera in the Management of Oral Submucous Fibrosis: A Prospective Clinical Study.

AIM: To determine the therapeutic efficacy of Kali haldi in the management of Oral submucous Fibrosis (OSMF) v/s steroid therapy. MATERIALS AND METHODS: A clinical prospective study was conducted on 42 patients of oral submucous fibrosis were equally divided into 2 groups. Group A patients were treated with a mixture of powdered Kali Haldi and aloe vera gel in equal ratio 3 times a day for 3 months. Group B patients were treated with intralesional injection of hydrocortisone and hyaluronidase for 6 weeks with oral antioxidant supplements for 3 months. Burning sensation, cheek flexibility, mouth opening, and tongue protrusion were evaluated before, during, and after treatment at an interval of 15 days, 1 month, 2, month and 3 months. RESULTS: Statistically significant results were obtained at the end of 3 months duration for both the groups (P < 0.001). The Symptomatic correction was more evident in the case of Group A patients than Group B. Response of the ayurvedic regimen was potentially better as compared to the regular steroid therapy. CONCLUSION: The study concludes that Combination therapy works wonders in the case of OSMF in stages I, II, III and can be a good option, comparatively safe and with negligible side effects, but potent and equally effective management of oral submucous fibrosis. Henceforth, it will be better to do such kinds of studies on a vast scale including larger samples and longer duration to check the efficacy and durability of this ancient ayurvedic regimen.

Dichotic listening performance and interhemispheric integration after administration of hydrocortisone.

Chronic stress has been shown to have long-term effects on functional hemispheric asymmetries in both humans and non-human species. The short-term effects of acute stress exposure on functional hemispheric asymmetries are less well investigated. It has been suggested that acute stress can affect functional hemispheric asymmetries by modulating inhibitory function of the corpus callosum, the white matter pathway that connects the two hemispheres. On the molecular level, this modulation may be caused by a stress-related increase in cortisol, a major stress hormone. Therefore, it was the aim of the present study to investigate the acute effects of cortisol on functional hemispheric asymmetries. Overall, 60 participants were tested after administration of 20 mg hydrocortisone or a placebo tablet in a cross-over design. Both times, a verbal and an emotional dichotic listening task to assess language and emotional lateralization, as well as a Banich-Belger task to assess interhemispheric integration were applied. Lateralization quotients were determined for both reaction times and correctly identified syllables in both dichotic listening tasks. In the Banich-Belger task, across-field advantages were determined to quantify interhemispheric integration. While we could replicate previously reported findings for these tasks in the placebo session, we could not detect any differences in asymmetry between hydrocortisone and placebo treatment. This partially corroborates the results of a previous study we performed using social stress to induce cortisol increases. This suggests that an increase in cortisol does not influence dichotic listening performance on a behavioral level. As other studies reported an effect of stress hormones on functional hemispheric asymmetries on a neuro-functional level, future research using neuronal imaging methods would be helpful in the characterization of the relation of hemispheric asymmetries and stress hormones.

Acute Illness and Death in Children With Adrenal Insufficiency.

Background: Adrenal Insufficiency (AI) can lead to life-threatening Adrenal Crisis (AC) and Adrenal Death (AD). Parents are trained to prevent, recognise and react to AC but there is little available information on what parents are actually doing at home to manage symptomatic AI. Methods: Three approaches were taken: (A) A retrospective analysis of patient characteristics in children and young people with AD over a 13-year period, (B) An interview-aided questionnaire to assess the circumstances around AC in children currently in our adrenal clinic, and (C) a separate study of parent perceptions of the administration of parenteral hydrocortisone. Results: Thirteen patients died (median age 10 years) over a thirteen-year period resulting in an estimated incidence of one AD per 300 patient years. Those with unspecified adrenal insufficiency were overrepresented (P = 0.004). Of the 127 patients contacted, thirty-eight (30%) were identified with hospital attendance with AC. Responses from twenty patients (median age 7.5 years) with AC reported nausea/vomiting (75%) and drowsiness (70%) as common symptoms preceding AC. All patients received an increase in oral hydrocortisone prior to admission but only two received intramuscular hydrocortisone. Questionnaires revealed that 79% of parents reported confidence in the administration of intramuscular hydrocortisone and only 20% identified a missed opportunity for injection. Conclusions: In children experiencing AC, parents followed 'sick day' guidance for oral hydrocortisone, but rarely administered intramuscular hydrocortisone. This finding is discrepant from the 79% of parents who reported confidence in this task. Local training programmes for management of AC are comprehensive, but insufficient to prevent the most serious crises. New strategies to encourage use of parenteral hydrocortisone need to be devised.

A novel bedtime pulsatile-release caffeine formula ameliorates sleep inertia symptoms immediately upon awakening.

Sleep inertia is a disabling state of grogginess and impaired vigilance immediately upon awakening. The adenosine receptor antagonist, caffeine, is widely used to reduce sleep inertia symptoms, yet the initial, most severe impairments are hardly alleviated by post-awakening caffeine intake. To ameliorate this disabling state more potently, we developed an innovative, delayed, pulsatile-release caffeine formulation targeting an efficacious dose briefly before planned awakening. We comprehensively tested this formulation in two separate studies. First, we established the in vivo caffeine release profile in 10 young men. Subsequently, we investigated in placebo-controlled, double-blind, cross-over fashion the formulation's ability to improve sleep inertia in 22 sleep-restricted volunteers. Following oral administration of 160 mg caffeine at 22:30, we kept volunteers awake until 03:00, to increase sleep inertia symptoms upon scheduled awakening at 07:00. Immediately upon awakening, we quantified subjective state, psychomotor vigilance, cognitive performance, and followed the evolution of the cortisol awakening response. We also recorded standard polysomnography during nocturnal sleep and a 1-h nap opportunity at 08:00. Compared to placebo, the engineered caffeine formula accelerated the reaction time on the psychomotor vigilance task, increased positive and reduced negative affect scores, improved sleep inertia ratings, prolonged the cortisol awakening response, and delayed nap sleep latency one hour after scheduled awakening. Based on these findings, we conclude that this novel, pulsatile-release caffeine formulation facilitates the sleep-to-wake transition in sleep-restricted healthy adults. We propose that individuals suffering from disabling sleep inertia may benefit from this innovative approach.Trials registration: NCT04975360.

Ketoconazole for the Treatment of Docetaxel-Naïve Metastatic Castration-Resistant Prostate Cancer (mCRPC): A Systematic Review.

OBJECTIVE: This systematic review aimed to determine the efficacy of ketoconazole in the treatment of metastatic castration-resistant prostate cancer (mCRPC). MATERIALS AND METHODS: A literature search was performed on four databases of PubMed, Google Scholar, Cochrane Database of Systematic Reviews, and Directory of Open Access Journals (DOAJ). The initial search resulted in 602 articles, which were progressively eliminated based on duplication, irrelevancy, and unsuitable methodology. A total of seventeen articles were included in the final analysis, including four randomized controlled trials, nine retrospective cohorts, and four prospective cohorts, with a total population of 1,095 patients. A 200-400 mg, tid dose of ketoconazole was used in these studies along with corticoid replacement therapy with hydrocortisone, 20-30 mg in the morning and 10-20 mg in the evening, or prednisone, 5 mg, bid. RESULTS: Based on our findings, 8 out of 17 studies reported PSA decrease of >50% in approximately half of the population, with a more significant PSA response at 400 mg ketoconazole dosage, and the average progression-free survival (PFS) of 2.6-14.5 months, or time to progression of 3.2-6.7 months. CONCLUSION: Ketoconazole with corticosteroid could be an effective alternative for the treatment of mCRPC with a satisfactory PSA response and disease progression.

[Spontaneous Hypoglycemia: A Diagnostic Challenge]. / Spontanhypoglykämien: Eine diagnostische Herausforderung.

HISTORY: A 59-year-old woman presented for an endocrinological evaluation of recurrent spontaneous hypoglycemia. The complaints always regressed after carbohydrate intake. Due to classic congenital adrenal hyperplasia, the patient received substitution therapy with hydrocortisone for decades. FINDINGS AND DIAGNOSIS: The patient was in good general condition and slightly overweight. The blood glucose at the time of admission was 87 mg/dl. The cortisol and adrenocorticotropic hormone (ACTH) under substitution with delayed-release hydrocortisone were unremarkable. The mixed-meal tolerance test (MMTT, standardized breakfast test) showed no reactive hypoglycemia. In the subsequent 72-hour fast, symptomatic hypoglycemia of 46 mg/dl was demonstrated after 36 hours. The insulin secretion was suppressed. The low cortisol as well as the high ACTH indicated an undersupply of hydrocortisone at this time. THERAPY AND COURSE: Initially, the morning dose of delayed-release hydrocortisone was increased. However, this had no effect on blood glucose. Therefore, hydrocortisone was also prescribed at night. CONCLUSION: In addition to endogenous hyperinsulinism, a disturbance of the contrainsulinergic hormones can also be responsible for spontaneous hypoglycemia.The MMTT and the 72-hour fast test should be used for diagnosis. It is important to ensure that hormone analysis is carried out immediately in hypoglycemia. The ratio of insulin, C-peptide and proinsulin to blood glucose and the constellation of counter-regulatory hormones such as cortisol, ACTH, growth hormone, Insulin-like growth factor 1 (IGF-1) and catecholamines can provide information about the etiology of hypoglycemia.

Corticosteroids in critical COVID-19: Are all corticosteroids equal?

BACKGROUND: The hyperinflammation seen as part of a dysregulated immune response to SARS-CoV-2 in its most severe form leads to acute respiratory distress syndrome (ARDS), multiorgan failure and death. Corticosteroid therapy targets this hyperinflammation, otherwise known as a cytokine storm. It is the only therapeutic agent to date with a mortality benefit, with clear guidelines from national and international health authorities guiding its use. Objectives. To compare severity-of-illness indices, survival, length of intensive care unit (ICU) stay and potential ICU complications in patients treated with different corticosteroid regimens (high-dose hydrocortisone, high-dose methylprednisolone and lower-dose dexamethasone). Methods. In this single-centre descriptive retrospective observational study of a cohort of patients with severe COVID-19 admitted to a COVID-dedicated ICU, we compared patients treated with the three different corticosteroid regimens. Results. In 242 cases we could not demonstrate any statistically or clinically significant difference in the outcome of patients with critical COVID-19 treated with high-dose intravenous hydrocortisone (n=88) or methylprednisolone (n=46) compared with a relatively lower dose of dexamethasone (n=108). The survival rates were 38.6%, 39.1% and 33.3%, respectively (p=0.68). Patients treated with methylprednisolone tended to have a shorter length of ICU stay (median (interquartile range) 6 (4 - 10), 4 (2 - 8) and 5 (2 - 8) days; p=0.015) and fewer episodes of nosocomial sepsis (47.7%, 32.6% and 48.1%; p=0.01). Conclusions. Hydrocortisone or methylprednisolone can be given as an alternative to dexamethasone in the management of critical COVID-19, and this is a feasible alternative, especially in resource-constrained settings.

Bradicardia sinusal inducida por corticoesteroides en un niño con insuficiencia suprarrenal y septicemia / Corticosteroid-induced sinus bradycardia in a young boy with adrenal insufficiency and sepsis

La bibliografía no incluye frecuentemente alteraciones en el ritmo cardíaco de los pacientes que reciben corticoesteroides; se desconoce su mecanismo exacto. En este artículo, presentamos el caso de un paciente con bradicardia sinusal asociada con una dosis de estrés de corticoesteroides. Se ingresó a un niño de 9 años con antecedentes de panhipopituitarismo con gastroenteritis y neumonía y presentó choque septicémico el día de la hospitalización. El tratamiento con líquidos intravenosos, dosis de estrés de hidrocortisona y antibióticos permitió la recuperación. Sin embargo, luego se documentó bradicardia sinusal con una frecuencia cardíaca de 45 latidos por minuto. Esta se resolvió después de reducir gradualmente la hidrocortisona. La bradicardia sinusal inducida por corticoesteroides es un efecto adverso que suele resolverse tras interrumpir el tratamiento. Se debe considerar el monitoreo hemodinámico en estos casos. Este es el primer informe de bradicardia sinusal posterior al uso de hidrocortisona en niños con insuficiencia suprarrenal

The literature does not commonly describe cardiac rhythm disturbances, including bradycardia, in patients who are receiving corticosteroids, and the exact mechanism of such disturbances remains unknown. Herein, we present a case of sinus bradycardia associated with stress-dose corticosteroid therapy. A nine-year-old boy with a history of panhypopituitarism was admitted with gastroenteritis and pneumonia and developed septic shock on the day of admission. Management using intravenous fluids, stress doses of hydrocortisone, and antibiotics resulted in full recovery. However, within 24 hours following treatment, sinus bradycardia was documented, with a heart rate of 45 beats per minute (BPM). The bradycardia resolved after the dose of hydrocortisone was decreased gradually. Corticosteroidinduced sinus bradycardia is an adverse effect that usually resolves after corticosteroid treatment is discontinued. During stress-dose corticosteroid therapy, hemodynamic monitoring should be considered. To our knowledge, this is the first report of sinus bradycardia following the use of hydrocortisone in children who have adrenal insufficiency.

Treatment of subcutaneous nodules after infusion of apomorphine; a biopsy-controlled study comparing 4 frequently used therapies.

This study aimed to provide clinical evidence for existing treatments of subcutaneous nodules after subcutaneous infusion of apomorphine, using a biopsy-controlled prospective crossover design of four treatments. We demonstrated that dilution of apomorphine significantly improved patient satisfaction, while subcutaneous hydrocortisone reduced nodule size, however with no differences in the histopathology.

[Drug-induced toxidermia in a patient receiving hydroxychloroquine as systemic therapy for primary Gougerot-Sjögren syndrome: a case report]. / Toxidermie médicamenteuse sous hydroxychloroquine pour traitement systémique d'un syndrome de Gougerot-Sjögren primaire: à propos d'un cas.

We here report the case of a 41-year-old female patient with maculopapular rash occurring a week after receiving hydroxychloroquine 400 mg for primary Gougerot-Sjögren syndrome with articular involvement. The patient had more than 1-year history of idiopathic minimal glomerular lesion, effectively treated with corticosteroid therapy. Maculopapular rashes resolved after hydroxychloroquine treatment was stopped and the patient was given hydrocortisone and desloratadine. Our case highlights the importance of prescribing low dose hydroxychloroquine in subjects with a history of kidney disease as well as of raising awareness and educating patients about side effects of hydroxychloroquine.

Addison's disease as a primary manifestation of extrapulmonary tuberculosis; A case report.

Tuberculosis remains an important public health problem globally. Addison's disease due to bilateral adrenal Tuberculosis as the primary manifestation of Extrapulmonary Tuberculosis is a very rare clinical entity. Previously healthy 52 years old male presented with increasing darkening of the skin, dizziness, loss of weight, loss of appetite, generalized weakness for one year and diarrhoea, vomiting for 3 months. Patient did not have any history of exposure to Tuberculosis. Physical examination revealed a hyposthenic man with generalized hyperpigmentation especially on the face, oral mucosa, palmer crease, and knuckles. Investigations revealed high erythrocyte sedimentation rate, persistent hyponatremia, and strongly positive mantoux test. Short Synacthen test confirmed the adrenal insufficiency. Ultrasound scan of the abdomen found to have bilaterally enlarged adrenal glands. Contrast-Enhanced Computed Tomography of abdomen confirmed the bilaterally enlarged adrenal glands. Magnetic resonance imaging brain has done, it was normal with no evidence of pituitary masses. Then Computed Tomography guided biopsy has done from left adrenal gland. Histology of biopsy report was compatible with Tuberculosis. With the evidence of above finding this patient diagnosed to have Addison's disease due to tuberculosis of bilateral adrenal glands. Anti-Tuberculosis Treatment started and continued for six months. Hydrocortisone and Fludrocortisone started. When there is an adrenal insufficiency, it should be always considered the possibility of existence of TB even failure to isolate bacillus Mycobacterium, failure to identify epidemiological exposure.

Topical corticosteroids for phimosis in children: a network meta-analysis of randomized clinical trials.

BACKGROUND: Corticosteroids and hyaluronidase are trialed for treating phimosis in children. We carried out the present network meta-analysis to compare the therapeutic effect of these drugs. METHODS: Electronic databases were searched for appropriate randomized clinical trials. Odds ratio (OR) with 95% confidence intervals (95% CI) was used as the effect estimate. A random-effects model was used for generating the pooled estimates. Rankogram plot was used for ranking the drugs. MAIN OUTCOME MEASURES: Proportions of patients with remission (partial/complete) and with complete remission. RESULTS: Mometasone (OR 6.53, 95% CI 2.85, 14.96), betamethasone/hyaluronidase (OR 12.1, 95% CI 4.27, 34.49), triamcinolone (OR 19.15, 95% CI 4.47, 81.96), dexamethasone (OR 21.38, 95% CI 5.71, 79.98), betamethasone (OR 23.02, 95% CI 6.92, 79.54), hydrocortisone (OR 23.2, 95% CI 5.91, 91.02) and methylprednisolone (OR 50.47, 95% CI 4.45, 572.72) were observed with significantly higher proportions of patients with remission (partial/complete) compared to placebo. Dexamethasone, triamcinolone, betamethasone, betamethasone/hyaluronidase, clobetasol, mometasone, and hydrocortisone were observed with significantly higher proportions of patients with complete remission compared to placebo. Beclomethasone was not observed to be superior to either placebo or other drugs. Rankogram plot revealed methylprednisolone followed by hydrocortisone had the maximum statistical probability of being 'the best' in the pool for remission and betamethasone followed by hydrocortisone for complete remission. CONCLUSION: Topical methylprednisolone, hydrocortisone, and betamethasone were observed with better clinical resolution of phimosis compared to other corticosteroids. Very high potent corticosteroids like beclomethasone and clobetasol were not observed with superior benefits compared to other corticosteroids. Considering low-potency, hydrocortisone shall be preferred until further evidence emerges.